Compositions and methods for treatment of neurological disorders

Abstract

Described herein are compositions comprising, and methods for using, biocompatible cold slurries and methods of administering the same to provide reversible inhibition of peripheral nerves in a subject in need thereof.

The invention claimed is: 
     
       1. A method of providing reversible inhibition of one or more peripheral nerves by tissue cooling to a subject in need thereof, said method comprising:
 (1) accessing tissue comprising one or more peripheral nerves; and 
 (2) injecting a biocompatible ice slurry into or around the one or more peripheral nerves, wherein: 
 the biocompatible ice slurry cools the one or more peripheral nerves for a duration sufficient to inhibit the one or more peripheral nerves in the subject; and 
 said inhibition is reversible. 
 
     
     
       2. The method of  claim 1 , wherein the biocompatible ice slurry comprises ice particles and one or more of a lactated Ringer's solution, an electrolyte solution, or a lactated electrolyte solution. 
     
     
       3. The method of  claim 2 , wherein the biocompatible ice slurry further comprises at least one of:
 hetastarch; 
 dextrose; 
 about 0.1% to about 20% glucose; 
 about 0.1% to about 20% glycerol; or 
 about 0.1% to about 6% hetastarch. 
 
     
     
       4. The method of  claim 1 , wherein the biocompatible ice slurry comprises ice particles and saline. 
     
     
       5. The method of  claim 1 , wherein the biocompatible ice slurry further comprises at least one of:
 about 0.1% to about 20% dextrose; 
 about 0.1% to about 5% ethanol; or 
 about 0.1% to about 10% poly vinyl alcohol. 
 
     
     
       6. The method of  claim 1 , wherein the biocompatible ice slurry further comprises at least one sugar, ion, polysaccharide, lipid, oil, lysolecithin, amino acid, caffeine, surfactant, antimetabolite, detergent, or a combination thereof. 
     
     
       7. The method of  claim 6 , wherein at least one of the following applies:
 the at least one sugar is glucose, mannitol, hetastarch, sucrose, sorbitol, or a combination thereof; 
 the at least one ion is calcium, potassium, hydrogen, chloride, magnesium, sodium, lactate, phosphate, zinc, sulfur, nitrate, ammonium, carbonate, hydroxide, iron, barium, salts, or a combination thereof; 
 the at least one oil is canola oil, coconut oil, corn oil, cottonseed oil, flaxseed oil, olive oil, palm oil, peanut oil, safflower oil, soybean oil, sunflower oil, or a combination thereof; 
 the at least one surfactant is a detergent; or 
 the at least one detergent is at least one of deoxycholate, sodium tetradecyl sulphate, polidocanol, sodium tetradecyl sulphate, polidocanol, polysorbate 20 (polyoxyethylene (20) sorbitan monolaurate), polysorbate 40 (polyoxyethylene (20) sorbitan monopalmitate), polysorbate 60 (polyoxyethylene (20) sorbitan monostearate), polysorbate 80 (polyoxyethylene (20) sorbitan monooleate), a sorbitan ester, a poloxamer, or a combination thereof. 
 
     
     
       8. The method of  claim 1 , wherein the biocompatible ice slurry comprises a peritoneal dialysis solution. 
     
     
       9. The method of  claim 1 , wherein injecting the biocompatible ice slurry into or around the one or more peripheral nerves comprises providing the biocompatible ice slurry along a perineural sheath of the one or more peripheral nerves. 
     
     
       10. The method of  claim 1 , wherein the one or more peripheral nerves are somatic nerves. 
     
     
       11. The method of  claim 10 , wherein the somatic nerves are sensory nerves, motor nerves, cranial nerves, or spinal nerves. 
     
     
       12. The method of  claim 1 , wherein the biocompatible ice slurry cools the one or more peripheral nerves to between about 5° C. and about −40° C. 
     
     
       13. The method of  claim 1 , wherein the biocompatible ice slurry has a first equilibration temperature of between about 4° C. and about −30° C. 
     
     
       14. The method of  claim 13 , wherein the biocompatible ice slurry has a second equilibration temperature of between about 2° C. and about −30° C. 
     
     
       15. The method of  claim 1 , wherein the biocompatible ice slurry comprises ice particles that are spherical or round with a diameter of about 1 mm to about 0.01 mm. 
     
     
       16. The method of  claim 1 , wherein the biocompatible ice slurry further comprises an agent selected from the group consisting of a vasoconstricting agent, a corticosteroid, a nonsteroidal anti-inflammatory drug (NSAID), an anesthetic, a glucocorticoid, a lipoxygenase inhibitor, and combinations thereof. 
     
     
       17. The method of  claim 16 , wherein the vasoconstricting agent is epinephrine or norepinephrine. 
     
     
       18. The method of  claim 16 , wherein the anesthetic is selected from the group consisting of lidocaine, bupivacaine, prilocaine, tetracaine, procaine, mepivacaine, etidocaine, N-ethyllidocaine, QX-314, and combinations thereof. 
     
     
       19. The method of  claim 1 , wherein the one or more peripheral nerves are selected from the group consisting of a cutaneous nerve, a trigeminal nerve, an ilioinguinal nerve, an intercostal nerve, an interscalene nerve, a supraclavicular nerve, an infraclavicular nerve, an axillary nerve, a paravertebral nerve, a transverse abdominis nerve, a genitofemoral nerve, a lumbar plexus nerve, a femoral nerve, a pudendal nerve, a celiac plexus nerve, and a sciatic nerve. 
     
     
       20. The method of  claim 1 , wherein the biocompatible ice slurry is injected into or around the one or more peripheral nerves of the subject by tumescent pumping of the slurry. 
     
     
       21. The method of  claim 1 , further comprising administering pressure to reduce blood flow at the site of injection. 
     
     
       22. The method of  claim 1 , further comprising monitoring the biocompatible ice slurry by ultrasound or imaging. 
     
     
       23. The method of  claim 1 , wherein the inhibition is reversed after about 5 months or less. 
     
     
       24. The method of  claim 1 , wherein the subject suffers from hyperhidrosis disorder. 
     
     
       25. The method of  claim 1 , further comprising cooling a tissue surrounding the one or more peripheral nerves prior to injecting, during, or after injecting the biocompatible ice slurry.